Setback can truly darken our times... Just after my return from being a FEBS LTF I have spent almost 3 challenging years with setting up a new BacMAM lab, purify protein and measure it. I am not saying sometimes I had not thought of simply quit and open a grocery store or make some graphics online whatever that would make me instantly happy, but then I went on. I guess classical psychology might help in such situations, saying that beyond a certain point you just run around the same thoughts, you have to break out and reach out to people, experts, even outsiders. I visited my FEBS LTF supervisor, also asked help form my current PI and finally convinced him to install collaboration with a foreign lab. I went to that very site and watched a postdoc every minute doing his thing and made notes of everything. It actually was not even quite clear afterwards what was fundamentally wrong with our approach, a bad (though commercial!!) plasmid, not the quite reagent, different cell lines, whatever but at the end it just started to work... Such a relief. Do not be shy, ask for help, sometimes you are doing all good and yet the problem lies in some irrational details.